A New Inflammatory Prognostic Index, Based on C-reactive Protein, the Neutrophil to Lymphocyte Ratio and Serum Albumin is Useful for Predicting Prognosis in Non-Small Cell Lung Cancer Cases

Dirican, Nigar,Dirican, Ahmet,Anar, Ceyda,Atalay, Sule,Ozturk, Onder,Bircan, Ahmet,Akkaya, Ahmet,Cakir, Munire Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.12

Purpose: We aimed to establish an inflammatory prognostic index (IPI) in early and advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze its predictive value for NSCLC survival. Materials and Methods: A retrospective review of 685 patients with early and advanced NSCLC diagnosed between 2009 and 2014 was conducted with collection of clinical, and laboratory data. The IPI was calculated as C-reactive protein ${\times}$ NLR (neutrophil/ lymphocyte ratio)/serum albumin. Univariate and multivariate analyses were performed to assess the prognostic value of relevant factors. Results: The optimal cut-off value of IPI for overall survival (OS) stratification was determined to be 15. Totals of 334 (48.8%) and 351 (51.2%) patients were assigned to high and low IPI groups, respectively. Compared with low IPI, high IPI was associated with older age, greater tumor size, high lymph node involvement, distant metastases, advanced stage and poor performance status. Median OS was worse in the high IPI group (low vs high, 8.0 vs 34.0 months; HR, 3.5; p<0.001). Progression free survival values of the patients who had high vs low IPI were determined 6 months (95% CI:5.3-6.6) and 14 months (95% CI:12.1-15.8), respectively (HR; 2.4, P<0.001). On multivariate analysis, stage, performance status, lactate dehydrogenase and IPI were independent prognostic factors for OS. Subgroup analysis showed IPI was generally a significant prognostic factor in all clinical variables. Conclusion: The described IPI may be an inexpensive, easily accessible and independent prognostic index for NSCLC patients, useful for clinical practice.

Treatment of Metastatic Colorectal Cancer With or Without Bevacizumab: Can the Neutrophil/Lymphocyte Ratio Predict the Efficiency of Bevacizumab?

Dirican, Ahmet,Varol, Umut,Kucukzeybek, Yuksel,Alacacioglu, Ahmet,Erten, Cigdem,Somali, Isil,Can, Alper,Demir, Lutfiye,Bayoglu, Ibrahim Vedat,Akyol, Murat,Yildiz, Yasar,Koyuncu, Betul,Coban, Eyup,Tarh Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

Background: The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. Materials and Methods: A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients were retrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. Results: Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). Conclusions: We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumab-based treatments in mCRC patients.

Prognostic and Predictive Value of Hematologic Parameters in Patients with Metastatic Renal Cell Carcinoma: Second Line Sunitinib Treatment Following IFN-alpha

Dirican, Ahmet,Kucukzeybek, Yuksel,Erten, Cigdem,Somali, Isil,Demir, Lutfiye,Can, Alper,Payzin, Kadriye Bahriye,Bayoglu, Ibrahim Vedat,Akyol, Murat,Yildiz, Yasar,Koseoglu, Mehmet,Alacacioglu, Ahmet,Ta Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

Background: Long-term survival is a problem with locally advanced and metastatic renal cell carcinomas. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, but data on sunitinib use as a second line treatment in metastatic renal cell carcinoma (mRCC) are limited. Prognostic and predictive value of peripheral blood markers has been shown for many cancers. Materials and Methods: Efficacy and safety profiles of sunitinib after interferon alpha (IFN-${\alpha}$) were evaluated based on retrospective data for 23 patients with mRCC. Hematological parameters (neutrophils, lymphocytes, platelets, mean platelet volume, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio) were recorded at the time of metastasis. It was evaluated whether hematological parameters were prognostic and predictive factors. Results: Median progression-free survival (PFS) time was 16.5 months (95%CI: 0-34.5). Median overall survival (OS) time was 25.7 months (95%CI: 10.8-40.0). Most common side effects were neutropenia (52.2%), stomatitis (26.1%) and hand-food syndrome (26.1%). PFS was found 3.13 vs 17.1 months in patients with neutrophil / lymphocyte ratio (NLR)>3 vs $NLR{\leq}3$ (p:0.012). Median OS was 6.96 vs 27.1 months in patients with NLR>3 vs $NLR{\leq}3$ (p:0.001).While 75% of patients who responded to sunitinib had $NLR{\leq}3$, in 72% of patients with no response to sunitinib NLR>3 was detected (p:0.036). The association between the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria and NLR was statistically significant (p:0.022). Conclusions: Data on second line sunitinib treatment following cytokine in mRCC are limited. In our study, we observed second line sunitinib treatment following IFN-${\alpha}$ to be effective and tolerable. NLRappeared to have prognostic and predictive value.

Depression, Anxiety and Sexual Satisfaction in Breast Cancer Patients and their Partners-Izmir Oncology Group Study

Alacacioglu, Ahmet,Ulger, Eda,Varol, Umut,Yildiz, Ibrahim,Salman, Tarik,Bayoglu, Vedat,Dirican, Ahmet,Demir, Lutfiye,Akyol, Murat,Yildiz, Yasar,Kucukzeybek, Yuksel,Ataman, Gorkem,Can, Huseyin,Alacacio Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: We aimed to investigate anxiety, depression and sexual satisfaction levels and the effects of depression and anxiety upon the sexual satisfaction of Turkish breast cancer patients and their partners. Materials and Methods: Data were collected from one hundred breast cancer patients and their partners, using three forms: one covering information about socio-demographic characteristics of the patients, the Hospital Anxiety and Depression Scale (HADs) and the Golombok-Rust Inventory of Sexual Satisfaction (GRISS). Results: The frequencies, avoidance and touch subscores were statistically significantly high in the patients. Among those with high anxiety scores, the frequency, communication, satisfaction, touch, and anorgasmic subscale scores of GRISS were found to be significantly high. Among the partners whose anxiety scores were high, only the premature ejaculation subscale was statistically significant. It was determined that for partners with higher depression scores, the communication, satisfaction, avoidance, premature ejaculation and erectile dysfunction subscores of GRISS were statistically higher compared to partners with lower depression scores. Conclusions: Patients' quality of life may be increased by taking precautions to reduce their and their partners' psychosocial and psychosexual concerns.

Adjuvant Chemotherapy and Prognostic Factors in Stage II Colon Cancer - Izmir Oncology Group Study

Kucukzeybek, Yuksel,Dirican, Ahmet,Demir, Lutfiye,Yildirim, Serkan,Akyol, Murat,Yildiz, Yasar,Bayoglu, Ibrahim Vedat,Alacacioglu, Ahmet,Varol, Umut,Salman, Tarik,Yildiz, Ibrahim,Can, Huseyin,Tarhan, M Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: Although adjuvant chemotherapy is a standard treatment in stage III colon cancer, its benefit is not as clear for stage II patients. In this retrospective analysis, we aimed to evaluate the survival of patients with low-risk stage II colon cancer, the efficacy of adjuvant chemotherapy in high-risk stage II colon cancer patients, and prognostic factors in stage II disease. Materials and Methods: One hundred and seventeen patients who were diagnosed with stage II colon cancer between January 2006 and December 2011 were included in the study. Patients were stratified into two groups as being low-risk and high-risk according to risk factors for stage II disease. Adjuvant 5-fluorouracil-based chemotherapy were administered to the patients with risk factors. Results: Ninety-four patients were treated with adjuvant chemotherapy due to high risk factors and 23 were monitored without treatment. Median follow-up time was 43 months. In terms of disease free survival and overall survival, adjuvant chemotherapy did not provide a statistically significant difference. Univariate analysis demonstrated that bowel obstruction was the major risk factor for shortened disease-free survival, while bowel perforation and perineural invasion were both negative prognostic factors for overall survival. Conclusions: The recommendation of adjuvant chemotherapy for stage II colon cancer is not clear. In our study, it was found that adjuvant chemotherapy did not contribute to survival in high-risk stage II patients. Due to the fact that prognosis of stage II patients is good, many more patients will be needed for statistically significant differences in survival. Adjuvant chemotherapy containing 5 fluorouracil is being used to high-risk stage II patients although it is not a standard treatment approach.

Second-Line Irinotecan after Cisplatin, Fluoropyrimidin and Docetaxel for Chemotherapy of Metastatic Gastric Cancer

Kucukzeybek, Yuksel,Dirican, Ahmet,Erten, Cigdem,Somali, Isil,Can, Alper,Demir, Lutfiye,Bayoglu, Ibrahim Vedat,Akyol, Murat,Medeni, Murat,Tarhan, Mustafa Oktay Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Aim: Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in $\dot{I}$zmir, Turkey. Materials and Methods: We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/$m^2$ on each 21 days. Irinotecan (180 mg/$m^2$ on day 1), 5-FU (500 mg/$m^2$ on days 1-2) and leucovorin (LV; 60 mg/$m^2$ on days 1-2) as a combined regimen were given over a 14 day period. Results: Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression-free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. Conclusions: In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

First-Line Mono-Chemotherapy in Frail Elderly Patients with Metastatic Colorectal Cancer

Varol, Umut,Dirican, Ahmet,Yildiz, Ibrahim,Oktay, Esin,Degirmenci, Mustafa,Alacacioglu, Ahmet,Barutca, Sabri,Karabulut, Bulent,Uslu, Ruchan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Unlike for fit elderly metastatic colorectal cancer (mCRC) patients, general approaches to initial treatment for the frail older mCRC patients are not clear. Our aim was to evaluate the efficiency and safety of first-line single-agent treatment in one such group. Materials and Methods: We retrospectively evaluated mCRC patients aged 70 or older with an Eastern Cooperative Oncology Group performance score of 2. They had no prior treatment and underwent first-line single-agent capecitabine or other monotherapies until disease progression or unacceptable toxicity. Results: Thirty-six patients were included. Most (n:28, 77.8%) were treated with capecitabine. One patient achieved a complete response and 5 patients had a partial response for an overall response rate of 16.6%. Twelve patients (33.3%) remained stable. Median progression free survival was 5 months (confidence interval (CI), %; 3.59-6.40) and median overall survival was 10 months (95 CI%; 8.1-11.8). Grade 3-4 toxicity was found in 6 patients (16.6%). Febrile neutropenia was not observed and there were no toxicity-associated deaths. Conclusions: Capecitabine is a safe chemotherapeutic agent with moderate activity for first-line treatment of older metastatic colorectal cancer patients with limited performance status.

Cisplatin Plus Gemcitabine for Treatment of Breast Cancer Patients with Brain Metastases: a Preferential Option for Triple Negative Patients?

Erten, Cigdem,Demir, Lutfiye,Somali, Isil,Alacacioglu, Ahmet,Kucukzeybek, Yuksel,Akyol, Murat,Can, Alper,Dirican, Ahmet,Bayoglu, Vedat,Tarhan, Mustafa Oktay Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

Background: To assess the efficacy and tolerability of Cisplatin plus Gemcitabine combination in patients with brain metastases (BM) from breast cancer (BC). Materials and Methods: Eighteen BC patients with BM who were treated with Cisplatin plus Gemcitabine regimen between 2003-2011 were evaluated. Results: A median of 6 cycles of this regimen were received, in fifteen patients (83.3%) as first-line chemotherapy, in 2 as second-line and in 1 as third-line after diagnosis of BM. Dose reduction was performed in 11 (61.1%) patients; major reasons were neutropenia and leukopenia. Grade III neutropenia and Grade II trombocytopenia rates were 33.3% and 16.7% respectively. Overall response rate (ORR; complete+partial response rate) was 33.4% (n=6) for the entire study population; triple negative patients achieved an 66.6% ORR while hormone receptor (HR) positive patients had 25% and HER2 positive patients 12.5%. Median progression-free survival was 5.6 months (2.4-8.8 months, 95%CI) and longer in patients with triple negative breast cancer (TNBC) (median 7.4 months, 95%CI, 2.4-12.3 months) than the patients with other subtypes (median 5 months for HER2 positive and 3.6 months for HR positive patients). Median PFS of the patients with TNBC who received this regimen as first-line was 9.2 months (5.2-13.2 months, 95%CI). Conclusions: Cisplatin plus Gemcitabine may be a treatment option for patients with BM from breast cancer. Longer PFS and higher response rates are results that support the usage of this regimen especially for the triple negative subtype. However, further prospective and randomized trials are clearly required to provide more exact information.

Use of Oral Antidiabetic Drugs (Metformin and Pioglitazone) in Diabetic Patients with Breast Cancer: How Does It Effect on Serum Hif-1 Alpha and 8Ohdg Levels?

Ece, Harman,Cigdem, Erten,Yuksel, Kucukzeybek,Ahmet, Dirican,Hakan, Er,Oktay, Tarhan Mustafa Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Objective: The aim was to investigate indicators related to DNA damage and cancer pathogenesis in Type II diabetes cases with breast cancer. It was planned to evaluate the relationship between these markers with oral antidiabetic drugs. Research Design and Methods: Fourty patients and 10 healthy individuals were included in the study. HIF-$1{\alpha}$ and 8-OHdG are examined in blood samples taken from these individuals with an ELISA Kit. Statistical analysis of data was performed with 95% confidence using Windows package program SPSS 15.0. Results: HIF-$1{\alpha}$ parameters were found to be meaningfully higher in the patient group than the controls in both pretreatment and posttreatment periods (p<0.05). No significant differences in terms of 8-OHdG between patients and controls. However, posttreatment serum HIF-$1{\alpha}$ ve 8-OHdG levels was found lower than pretreatment levels in patients receiving metformin, but not with pioglitazone. Conversely, serum 8-OHdG levels decreased significantly in these patients. When patients were evaluated according to the treatment groups (pioglitazone vs. metfformin) no significant differences in terms of serum HIF-$1{\alpha}$ and 8-OHdG levels between treatment groups. Conclusions: HIF-$1{\alpha}$ levels decreased significantly in the patient group receiving metformin. However, there was no significant difference in terms of HIF-$1{\alpha}$ levels in the patients receiving pioglitazone.

Does Immunohistochemistry Provide Additional Prognostic Data in Gastrointestinal Stromal Tumors?

Demir, Lutfiye,Ekinci, Nese,Erten, Cigdem,Kucukzeybek, Yuksel,Alacacioglu, Ahmet,Somali, Isil,Can, Alper,Dirican, Ahmet,Bayoglu, Vedat,Akyol, Murat,Cakalagaoglu, Fulya,Tarhan, Mustafa Oktay Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Background: To investigate the predictive and prognostic effects of clinicopathologic and immunohistochemical (IHC) features in patients with gastrointestinal stromal tumours (GISTs). Materials and Methods: Fifty-six patients who were diagnosed with GIST between 2002 and 2012 were retrospectively evaluated. Relationships between clinicopathologic/immunohistochemical factors and prognosis were investigated. Results: Median overall survival (OS) of the whole study group was 74.9 months (42.8-107.1 months), while it was 95.2 months in resectable and 44.7 months in metastatic patients respectively (p=0.007). Epitheliolid tumor morphology was significantly associated with shortened OS as compared to other histologies (p=0.001). SMA(+) tumours were significantly correlated with low (<10/50HPF) mitotic activity (p=0.034). Moreover, SMA(+) patients tended to survive longer and had significantly longer disease-free survival (DFS) times than SMA (-) patients (37.7 months vs 15.9 months; p=0.002). High Ki-67 level (${\geq}30%$) was significantly associated with shorter OS (34 vs 95.2 months; 95%CI; p=0.001). CD34 (-) tumours were significantly associated with low proliferative tumours (Ki-67<%10) (p=0.026). Median PFS (progression-free survival) of the patients who received imatinib was 36 months (27.7-44.2 months). CD34 (-) patients had significantly longer PFS times than that of negative tumours; (50.8 vs 29.8 months; p=0.045). S100 and desmin expression did not play any role in predicting the prognosis of GISTs. Multivariate analysis demonstrated that ${\geq}10/50HPF$ mitotic activity/HPF was the only independent factor for risk of death in GIST patients. Conclusions: Despite the negative prognostic and predictive effect of high Ki-67 and CD34 expression, mitotic activity remains the strongest prognostic factor in GIST patients. SMA positivity seems to affect GIST prognosis positively. However, large-scale, multicenter studies are required to provide supportive data for these findings.